Researchers have cracked part of the code for an important gene function in familial Alzheimer's disease (FAD), an early-onset type of AD. Alzheimer's disease is the most common cause of dementia. Working with cells in culture that had been altered to overexpress the amyloid precursor protein (APP), the researchers were able to document that expression of a mutant form of the presenilin-1 (PS-1) protein caused a significant reduction in the amount of amyloid formed. This continuing study of the mechanisms of plaque formation, researchers believe, moves them ever closer to the possible development of novel drugs to intervene in the processes leading up to Alzheimer's dementia.
Naturally occurring mutations in PS-1 are found in about 40 percent of people with FAD. Previous studies have suggested that these inherited PS-1 gene mutations increase the amount of amyloid clipped out from the larger amyloid precursor protein, but no one could determine how that clipping occurred. Researchers named the elusive and not-well-understood enzyme that is involved in the clipping, gamma secretase. The current research suggests that either PS-1 may be the long sought gamma-secretase, or that PS-1 is essential for gamma secretase's ability to clip amyloid.
The study of mutated PS-1 protein was published in the April 8, 1999 issue of
Nature by Dr. Dennis J. Selkoe and his colleagues at Harvard Medical School and
Brigham and Women's Hospital, Boston, and the University of Tennessee, Memphis.
Their work focuses on the chemical events that may lead to the development of
brain damage and the symptoms of dementia. The National Institute on Aging
(NIA), and the National Institute of Neurological Disorders and Stroke (NINDS),
two components of the National Institutes of Health (NIH), funded the study.
In their search to explain why the amyloid fragments clump into plaques, which
surround the brain cells of Alzheimer's disease patients, Dr. Selkoe's group
Contact: Claudia Feldman and Margo Warren
301-496-1752 or 5751
NIH/National Institute on Aging